2MCR: Solution structure of ShK-like immunomodulatory peptide from Brugia malayi (filarial worm)

Citation:
Abstract
The voltage-gated potassium (Kv) 1.3 channel is widely regarded as a therapeutic target for immunomodulation in autoimmune diseases. ShK-186, a selective inhibitor of Kv1.3 channels, ameliorates autoimmune diseases in rodent models, and human phase 1 trials of this agent in healthy volunteers have been completed. In this study, we identified and characterized a large family of Stichodactyla helianthus toxin (ShK)-related peptides in parasitic worms. Based on phylogenetic analysis, 2 worm peptides were selected for study: AcK1, a 51-residue peptide expressed in the anterior secretory glands of the dog-infecting hookworm Ancylostoma caninum and the human-infecting hookworm Ancylostoma ceylanicum, and BmK1, the C-terminal domain of a metalloprotease from the filarial worm Brugia malayi. These peptides in solution adopt helical structures closely resembling that of ShK. At doses in the nanomolar-micromolar range, they block native Kv1.3 in human T cells and cloned Kv1.3 stably expressed in L929 mouse fibroblasts. They preferentially suppress the proliferation of rat CCR7(-) effector memory T cells without affecting naive and central memory subsets and inhibit the delayed-type hypersensitivity (DTH) response caused by skin-homing effector memory T cells in rats. Further, they suppress IFNgamma production by human T lymphocytes. ShK-related peptides in parasitic worms may contribute to the potential beneficial effects of probiotic parasitic worm therapy in human autoimmune diseases.
PDB ID: 2MCRDownload
MMDB ID: 138689
PDB Deposition Date: 2013/8/22
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Similar Structures:
Biological Unit for 2MCR: monomeric; determined by author
Molecular Components in 2MCR
Label Count Molecule
Protein (1 molecule)
1
Probable Zinc Metalloproteinase, Putative
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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